Electron Paramagnetic Resonance (EPR) is a spectroscopic technique that is analogous to Nuclear Magnetic Resonance (NMR). EPR spectroscopy detects species with unpaired electrons such as transition metal ions and free radicals, rather than the magnetic nuclei such as 1H, 13C, and 19F detected using NMR spectroscopy methods. Magnetic Resonance Imaging (MRI) employs magnetic field gradients to generate anatomic images from objects that have a significant amount of water protons therein. The contrast agent-induced spectral changes such as changes in spin-lattice relaxation (T1) and spin-spin relaxation (T2) times of protons provide functional information. Recently available biologically compatible free radical contrast agents have made in vivo EPR imaging feasible using methods similar to MRI methods. However, the spectral changes in EPR are much more sensitive to local environment than in MRI, making EPR imaging a potentially useful functional imaging technique.
EPR techniques may be executed in a continuous wave (CW) mode using a relatively slow field-swept mode, or by using pulses as in MRI in a constant magnetic field, which may obtain data much more quickly. However, pulsed EPR methods utilize paramagnetic spin probes having very narrow line widths to achieve sufficient capture of the impulse response of magnetization in the presence of magnetic field gradients for image formation. Numerous narrow line width spin probes based on triarylmethyl (trityl) radical are available that may be used for time-domain EPR imaging.
Spin echo Fourier transform imaging is a procedure in which a subject may be perfused with a narrow-line paramagnetic spin probe and then subjected to a 90°-t-180° or a general θ-t-2θ pulse pair. At a specified time from the first 90° pulse that depends on the timing of the second 180° pulse, an echo is received in which the echo peak height is attenuated by spin-spin relaxation. Fourier transform of the echo measured within a series of frequency encoding linear magnetic field gradients generates a spatial projection of the echo. A series of spatial projections generated as a function of the gradient vector orientation at equal angular intervals in a plane generated projections that may be subjected to filtered back projection to give a two-dimensional image of the object projected on to the plane of the gradient rotation. The plane of rotation of the linear magnetic field gradients may also be rotated in order to sweep a spherical volume centered on the object, and a two-step filtered back projection may be used to generate a three-dimensional image. The quality and resolution of the image depends on at least several factors including but not limited to the line width of the spin probe, the magnitude of the gradient, and the spacing of the gradient rotation angles.
The second pulse refocuses any line broadening brought about by the gradient-induced T2* and the intrinsic magnetic susceptibility of the subject. Images formed by the filtered back projection from echoes are weighted in contrast by the relaxation time T2, which depends linearly on the oxygen content at each spatial location within the subject. Quantitative oxymetric information may be derived from a series of T2-weighted images as a function of the echo time. Conventional 90°-180° spin echo pulse sequence images may be obtained by the filtered back-projection of the frequency-encoded projections obtained by the Fourier transform of spin echoes. The spin echo Fourier transform method yields oxymetric data that is well-suited for clinical applications, however the spatial resolution of the imaging is not of sufficient quality for EPR imaging.
Multi-gradient Single Point Imaging (SPI) is another approach to tissue imaging that utilizes pure phase encoding in which the oxymetric data are T2*-based. This approach relies on apparent line width evaluations that may be vulnerable to degradation due to factors including but not limited to the intrinsic magnetic susceptibility of the subject and non-homogeneity of the magnetic field that may be ameliorated using system-specific calibrations using reference standards. While SPI imaging gives superior spatial resolution, oxygen quantization in this procedure may need careful calibration to yield sufficiently accurate oxymetric results.
A need in the art exists for a tissue imaging method that combines the excellent spatial resolution of SPI imaging and the highly accurate oxymetric information obtainable using spin echo Fourier transform imaging procedures.